Cancers, Vol. 10, Pages 225: Geriatric Assessment in Older Patients with Acute Myeloid Leukemia

Cancers, Vol. 10, Pages 225: Geriatric Assessment in Older Patients with Acute Myeloid Leukemia

Cancers doi: 10.3390/cancers10070225

Authors: Kah Poh Loh Heidi D. Klepin

The incidence of acute myeloid leukemia (AML) increases with age, but the outcomes for older adults with AML are poor due to underlying tumor biology, poor tolerance to aggressive treatment, and the physiologic changes of aging. Because of the underlying heterogeneity in health status, treatment decisions are difficult in this population. A geriatric assessment (GA) refers to the use of various validated tools to assess domains that are important in older adults including physical function, cognition, comorbidities, polypharmacy, social support, and nutritional status. In older patients with cancer, a GA can guide treatment decision-making, predict treatment toxicity, and guide supportive care interventions. Compared to solids tumors, there is a relative lack of studies evaluating the use of a GA in older patients with AML. In this review, we will discuss the principles, common domains, feasibility, and benefits of GA, with a focus on older patients with AML that includes practical applications for clinical management.

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Surgical management of chronic genital lymphoedema

A 44-year-old man with a spinal cord injury was referred to a specialist urology service with a 7-year history of significant genital swelling. His condition had eluded diagnosis and was refractory to all previous treatments. The considerable swelling both impacted his quality of life and prevented the patient from adequately managing his neurogenic bladder. He was diagnosed with chronic idiopathic genital lymphoedema and underwent total scrotectomy, wide penile skin excision and split skin graft to the penile shaft. The patient made an excellent recovery. We present this unusual case with preoperative, intraoperative and postoperative images.

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Case of hepatic portal venous gas in an infant with hypertrophic pyloric stenosis

Hepatic portal venous gas is the presence of gas within the portal vein and its branches. A 4-week-old male infant presented with 1-week history of non-bloody, non-bilious projectile emesis. Examination was significant for an olive-shaped mass in the abdomen. Bloodwork showed hypokalaemic metabolic alkalosis. Abdominal ultrasound and radiograph was significant for portal venous gas and did not meet radiographic criteria for pyloric stenosis. He underwent upper endoscopy, which showed a narrowed, hypertrophic pylorus. The child underwent pyloromyotomy with resolution of his emesis. Hepatic portal venous gas (HPVG) is very rare and can be seen in the setting of hypertrophic pyloric stenosis. It is believed that an increase in intraluminal dilation and pressure subsequently moves gas from the intestinal mucosa venous system and lymphatics into the portal veins. The presence of HPVG in a well-appearing patient can be benign and should not prompt further testing nor delay treatment.

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Renal cell carcinoma with level 2 IVC thrombus

Description

A 40-year-old male patient, a chronic smoker for the last 10 years, presented with oedema of the lower legs and gross painless haematuria of 2 months duration. He also gave history of weight loss and loss of appetite. Physical examination revealed a right abdominal mass. Complete blood haemogram was normal. A comprehensive metabolic evaluation including serum calcium levels, C-reactive protein, liver function and urinalysis was also found normal.

Multidetector CT scan showed a right renal tumour of size 8x8 cm involving upper and mid-pole with tumour thrombus extending from the renal vein (RV) into the infrahepatic inferior vena cava (IVC) (figure 1). CT angiography was further performed to confirm the vascularity and extent of RV thrombus as shown in figure 2.

Figure 1

Right renal cell carcinoma involving upper and mid-pole with tumour thrombus extending into infrahepatic inferior vena cava (IVC).

...

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CMV encephalitis in an immune-competent patient

After being admitted to hospital with atypical chest pain, a 61-year-old woman was noted to become lethargic and confused. She also developed global dysphasia. MRI was suggestive of encephalitis, and lumbar puncture was positive for cytomegalovirus (CMV) PCR. The patient was treated with intravenous ganciclovir and subsequent oral valganciclovir and she gradually made a reasonable recovery. While this infection is usually closely linked to immunosuppression, the patient was found to be HIV negative, and was not on any immunosuppressive therapy. Going through the patient's medical history revealed two possible risk factors which might have led to the development of CMV encephalitis: immunosuppression secondary to underlying poorly controlled diabetes mellitus; and previous admission to the intensive care unit which might have lead to CMV reactivation.

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EMT, stemness and tumor plasticity in aggressive variant neuroendocrine prostate cancers

Publication date: Available online 5 July 2018

Source: Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

Author(s): Rama Soundararajan, Anurag N. Paranjape, Sankar Maity, Ana Aparicio, Sendurai A. Mani

Abstract

Neuroendocrine/Aggressive Variant Prostate Cancers are lethal variants of the disease, with an aggressive clinical course and very short responses to conventional therapy. The age-adjusted incidence rate for this tumor sub-type has steadily increased over the past 20 years in the United States, with no reduction in the associated mortality rate. The molecular networks fueling its emergence and sustenance are still obscure; however, many factors have been associated with the onset and progression of neuroendocrine differentiation in clinically typical adenocarcinomas including loss of androgen-receptor expression and/or signaling, conventional therapy, and dysregulated cytokine function. "Tumor-plasticity" and the ability to dedifferentiate into alternate cell lineages are central to this process. Epithelial-to-mesenchymal (EMT) signaling pathways are major promoters of stem-cell properties in prostate tumor cells. In this review, we examine the contributions of EMT-induced cellular-plasticity and stem-cell signaling pathways to the progression of Neuroendocrine/Aggressive Variant Prostate Cancers in the light of potential therapeutic opportunities.

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Use of Enteral Nutrition for Gastrointestinal Bleeding Prophylaxis in the Critically Ill: Review of Current Literature

Abstract

Purpose of Review

This review provides a comprehensive overview of the etiology of stress-related mucosal disease, current acid suppression therapy recommendations, and the role enteral nutrition may play in disease prevention.

Recent Findings

Recent literature indicates enteral nutrition may prevent complications of stress-related mucosal disease by increasing splanchnic blood flow, enhancing gastrointestinal motility, and promoting cellular immunity and integrity through local nutrient delivery.

Summary

Stress-related mucosal disease is a common complication of hospitalization in the critically ill which may lead to overt gastrointestinal bleeding and enhanced mortality. High-risk patients have historically been prescribed acid suppression therapy, though enteral nutrition may also have a role in disease mitigation.

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The Role of Nutrition in Cognitive Function and Brain Ageing in the Elderly

Abstract

Purpose of Review

The purposes of this review were to examine literature published over the last 5 years and to evaluate the role of nutrition in cognitive function and brain ageing, focussing on the Mediterranean diet (MeDi), Dietary Approaches to Stop Hypertension (DASH), and Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diets.

Recent Findings

Results suggest that higher adherence to a healthy dietary pattern is associated with preservation of brain structure and function as well as slower cognitive decline, with the MIND diet substantially slowing cognitive decline, over and above the MeDi and DASH diets.

Summary

Whilst results to-date suggest adherence to a healthy diet, such as the MeDi, DASH, or MIND, is an important modifiable risk factor in the quest to develop strategies aimed at increasing likelihood of healthy brain ageing, further work is required to develop dietary guidelines with the greatest potential benefit for public health; a research topic of increasing importance as the world's population ages.

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Nutrition Education Services Described on National Cancer Institute (NCI)-Designated Cancer Center Websites

Abstract

For women diagnosed with breast cancer, healthy weight and enhanced nutrition may improve outcomes. The goal of this study is to examine the nutrition education services available on National Cancer Institute (NCI)-Designated Cancer Centers' websites. In 2017, websites of all 61 NCI-Designated Cancer Centers that provide adult clinical care were reviewed at least twice. Websites were analyzed for the existence and type of expert-directed nutrition education services for breast cancer survivors. Of the 61 websites analyzed, 49 (80%) provided information about nutrition education. Twenty (33%) included only nutrition counseling, three (5%) only nutrition classes, and 26 (42%) both counseling and classes. Forty-six websites included information about nutrition counseling; of these, 39 had an easily identifiable description. Thirty-seven class options were offered, 22% were specific to breast cancer, 16% to subgroups such as young women, 41% were nutrition-only classes, and 24% included skills education. Nutrition services are an important part of breast cancer treatment. This study demonstrated that most NCI-designated cancer centers offered counseling. However, the type of information that was offered varied and services were not always specific to patients with breast cancer. Further research is needed to confirm the presence of services, assess patient access, and demonstrate their efficacy in promoting optimal survivor outcomes.

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Comparison of SUVmax and SUVpeak based segmentation to determine primary lung tumour volume on FDG PET-CT correlated with pathology data

The aim of the study was to compare simple SUVmax and SUVpeak based segmentation methods for calculating the lung tumour volume, compared to a pathology ground truth.

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Impact of radiotherapy underutilisation measured by survival shortfall, years of potential life lost and disability-adjusted life years lost in New South Wales, Australia

Despite evidence of the benefits of radiotherapy (RT) in the treatment of cancer patients, its underutilisation has been reported for various tumour sites. The aim of this study was to estimate survival shortfall, 'years of potential life lost' (YPLL) and 'disability-adjusted life years lost' (DALY) to demonstrate the impact of radiotherapy underutilisation in Australia.

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Modified Friedman technique: a new proposed method of measuring glenoid version in the setting of glenohumeral dysplasia

Abstract

Background

Glenoid version angles are measured to objectively follow changes related to glenohumeral dysplasia in the setting of brachial plexus birth palsy. Measuring glenoid version on cross-sectional imaging was initially described by Friedman et al. in 1992. Recent literature for non-dysplastic shoulders advocates time-consuming reconstructions and reformations for an accurate assessment of glenoid version.

Objective

To compare Friedman's original method for measuring glenoid version to a novel technique we developed ("modified Friedman") with the reference standard of true axial reformations.

Materials and methods

With institutional review board approval, we retrospectively examined 30 normal and dysplastic shoulders obtained from magnetic resonance imaging examinations of 30 patients with an established diagnosis of brachial plexus birth palsy between January 2012 and September 2017. Four pediatric radiologists performed glenoid version measurements using Friedman's method, the modified Friedman method and a previously described true axial reformation method. The modified Friedman technique better accounts for scapular positioning by selecting a reference point related to the acromion-scapular body interface. Inter-rater reliability and inter-method agreement were assessed using intraclass correlation, paired t-tests and mixed linear model analysis. Equivalence tests between methods were performed per reader.

Results

Glenoid version measurements were significantly different when comparing Friedman's method to true axial reformations in normal (-10.8±5.7° [mean±standard deviation] vs. -8.8±5.3°; P≤0.001) and dysplastic shoulders (-34.6±17.7° vs. -28.1±17.5°; P≤0.001). Glenoid version measurements were not significantly different when comparing the modified Friedman's method to true axial reformations in normal (-6.3±5.8° vs. -8.8±5.3°; P=0.06) and dysplastic shoulders (-29.0±18.3° vs. -28.1±17.5°; P=0.06). Friedman's method was not equivalent to true axial reformations for measurements in dysplastic shoulders for all readers (P=0.68, 0.81, 0.86, 0.99); the modified Friedman method was equivalent to of true axial reformations for measurements in dysplastic shoulders for 3 of 4 readers (P≤0.001, P≤0.001, P≤0.001, P=0.10).

Conclusion

In glenohumeral dysplasia, the modified Friedman method and post-processed true axial reformations provide statistically similar and reproducible values. We propose that our modified Friedman technique can be performed in lieu of post-processed true axial reformations to generate glenoid version measurements.

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A rare case of seven siblings with Waardenburg syndrome: a case report

Waardenburg syndrome is a group of rare genetic conditions. It is determined by the absence of melanocytes from the eyes, hair, and skin. There are four types of Waardenburg syndrome with specific criteria to ...

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Bilateral septic arthritis of the sternoclavicular joint complicating infective endocarditis: a case report

Septic arthritis is an infectious disease that commonly affects weight-bearing or proximal joints such as the knee and the hip. The sternoclavicular joint is an unusual site of this entity. It usually occurs i...

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Preoperative sonographic evaluation of the defect size and the diaphragm rim in congenital diaphragmatic hernia — preliminary experience

Abstract

Background

Sonographic assessment before congenital diaphragmatic hernia repair has rarely been studied.

Objective

To evaluate the accuracy of preoperative ultrasound in measuring the defect size and in anticipating the presence of a rim and thereby to determine ultrasound's usefulness in informing the surgical approach for definitive repair of congenital diaphragmatic hernia.

Materials and methods

We performed a retrospective review of the medical records of seven children with left congenital diaphragmatic hernia who had undergone ultrasound and definitive repair between 2014 and 2017 at our institution.

Results

The estimated defect size by ultrasound to the actual defect size measured intraoperatively for each case were as follows: 23 × 25 mm to 20 × 26 mm (case 1); 23 × 30 mm to 20 × 30 mm (case 2); 43 × 25 mm to 30 × 30 mm (case 3); 21 × 23 mm to 20 × 25 mm (case 4); 19 × 24 mm to 10 × 30 mm (case 5); 32 × 33 mm to 30 × 50 mm (case 6); and almost total absence to 40 × 50 mm (case 7). Presence or absence of each part of the diaphragm rim evaluated by ultrasound was almost identical with the actual intraoperative findings. According to the ultrasound findings, we performed a successful thoracoscopic repair in cases 1–5 with relatively small defects and presence of all parts of the rim or absence of only posterolateral rim.

Conclusion

There was good concordance between ultrasound findings and operative findings regarding the size of the defect and presence or absence of the diaphragm rim.

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Preclinical models for precision oncology

Publication date: Available online 28 June 2018

Source: Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

Author(s): Maider Ibarrola-Villava, Andrés Cervantes, Alberto Bardelli

Abstract

Precision medicine approaches have revolutionized oncology. Personalized treatments require not only identification of the driving molecular alterations, but also development of targeted therapies and diagnostic tests to identify the appropriate patient populations for clinical trials and subsequent therapeutic implementation. Preclinical in vitro and in vivo models are widely used to predict efficacy of newly developed treatments. Here we discuss whether, and to what extent, preclinical models including cell lines, organoids and tumorgrafts recapitulate key features of human tumors. The potential of preclinical models to anticipate treatment efficacy and clinical benefit is also presented, using examples in different tumor types.

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Metabolic reprogramming for cancer cells and their microenvironment: Beyond the Warburg Effect

Publication date: Available online 28 June 2018

Source: Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

Author(s): Linchong Sun, Caixia Suo, Shi-ting Li, Huafeng Zhang, Ping Gao

Abstract

While metabolic reprogramming of cancer cells has long been considered from the standpoint of how and why cancer cells preferentially utilize glucose via aerobic glycolysis, the so-called Warburg Effect, the progress in the following areas during the past several years has substantially advanced our understanding of the rewired metabolic network in cancer cells that is intertwined with oncogenic signaling. First, in addition to the major nutrient substrates glucose and glutamine, cancer cells have been discovered to utilize a variety of unconventional nutrient sources for survival. Second, the deregulated biomass synthesis is intertwined with cell cycle progression to coordinate the accelerated progression of cancer cells. Third, the reciprocal regulation of cancer cell's metabolic alterations and the microenvironment, involving extensive host immune cells and microbiota, have come into view as critical mechanisms to regulate cancer progression. These and other advances are shaping the current and future paradigm of cancer metabolism.

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The emerging role of circRNAs and their clinical significance in human cancers

Publication date: Available online 19 June 2018

Source: Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

Author(s): Ling Qian, Shulin Yu, Zhen Chen, Zhiqiang Meng, Shenglin Huang, Peng Wang

Abstract

Circular RNA (circRNA), a recently discovered subclass of non-coding RNAs (ncRNAs), forms a covalently closed loop with neither a 5′ cap structure nor a 3′ polyadenylated tail. Generated from precursor mRNA (pre-mRNA) through "backsplicing" (a type of alternative RNA splicing), the majority of circRNAs are located in the cytoplasm and are widespread among living organisms. They are stable and conserved and exhibit spatiotemporal-specific expression. CircRNAs are known to be involved in the development and progression of multiple diseases, including cancer, by acting as microRNA (miRNA) sponges and by regulating processes such as transcription and translation. The extensively aberrant expression profiles of circRNAs in multiple cancerous tissues make these molecules promising diagnostic biomarkers and therapeutic targets for cancer. Here, we briefly review the characteristics, biogenesis, classification, and functions of circRNAs, with a particular focus on the role of circRNAs in various cancers.

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MEF2 and the tumorigenic process, hic sunt leones

Publication date: Available online 5 June 2018

Source: Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

Author(s): Eros Di Giorgio, Wayne W. Hancock, Claudio Brancolini

Abstract

While MEF2 transcription factors are well known to cooperate in orchestrating cell fate and adaptive responses during development and adult life, additional studies over the last decade have identified a wide spectrum of genetic alterations of MEF2 in different cancers. The consequences of these alterations, including triggering and maintaining the tumorigenic process, are not entirely clear. A deeper knowledge of the molecular pathways that regulate MEF2 expression and function, as well as the nature and consequences of MEF2 mutations are necessary to fully understand the many roles of MEF2 in malignant cells. This review discusses the current knowledge of MEF2 transcription factors in cancer.

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Targeting cancer's metabolic co-dependencies: A landscape shaped by genotype and tissue context

Publication date: Available online 23 May 2018

Source: Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

Author(s): Junfeng Bi, Sihan Wu, Wenjing Zhang, Paul S. Mischel

Abstract

Tumors cells reprogram their metabolism to fuel rapid growth. The ability to trace nutrient fluxes in the context of specific alterations has provided new mechanistic insight into the process of oncogenic transformation. A broad array of complementary genetic, epigenetic, transcriptional and translational mechanisms has been identified, revealing a metabolic landscape of cancer. However, cancer metabolism is not a static or uniform process, including within a single tumor. Tumor cells adapt to changing environmental conditions, profoundly shaping the enzymatic dependencies of individual cells. The underlying molecular mechanisms of adaptation, and the specific interactions between tumor genotype, oncogenic signaling, and tissue/biochemical context, remain incompletely understood. In this review, we examine dynamic aspects of how metabolic dependencies develop in cancer, shaped both by genotype and biochemical environment, and review how these interlaced processes generate targetable metabolic vulnerabilities. This article is part of a Special Issue entitled: Cancer Metabolism edited by Dr. Chi Van Dang.

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Control of metabolism by p53 – Cancer and beyond

Publication date: Available online 5 June 2018

Source: Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

Author(s): Christiaan F. Labuschagne, Fabio Zani, Karen H. Vousden

Abstract

p53 is an important tumour suppressor gene, with loss of p53 contributing to the development of most human cancers. However, the activation of p53 in response to stress signals underpins a role for p53 in diverse aspects of health and disease. Activities of p53 that regulate metabolism can play a role in maintaining homeostasis and protecting cells from damage – so preventing disease development. By contrast, either loss or over-activation of p53 can contribute to numerous metabolic pathologies, including aging, obesity and diabetes.

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MicroRNAs as potential liquid biopsy biomarkers in colorectal cancer: A systematic review

Publication date: Available online 29 May 2018

Source: Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

Author(s): Yuji Toiyama, Yoshinaga Okugawa, James Fleshman, C. Richard Boland, Ajay Goel

Abstract

Emerging evidence has demonstrated the feasibility of circulating miRNAs as robust non-invasive biomarkers for the diagnosis in colorectal cancer. The use of circulating miRNAs for the early detection of colorectal cancer (CRC) is of particular interest as it can offer a potential complementary approach to screening colonoscopy. However, the development of circulating miRNAs as "liquid biopsy" biomarkers for development into clinical screening tests has been hampered by several issues. In this article, we summarize the status of this field for the clinical utilization of miRNA biomarkers as liquid biopsies in colorectal cancer (CRC) and discuss their applications as screening tests for patients with colorectal adenoma (CRA) and CRC. Herein, we undertook a systematic search for citations in PubMed and the Cochrane Database from January 1, 2002 through December 31, 2017 as electronic sources for this study. All published studies were screened with no restriction on language, date, or country. We used database-specific combinations of the following index terms and text words, including: microRNA, colorectal cancer, serum, plasma, and exosomes. Based upon these searches, we summarize the progress and salient features of the current state of knowledge of miRNA diagnostic biomarkers in CRC, and focuses on the articles that attempt to optimize ideal methodologies to further advance their as liquid biopsies for clinical use. We conclude that the field of noncoding RNAs, particularly for the clinical use of miRNAs as liquid biopsy assays is maturing rapidly, and it is highly promising that these genomic signatures will likely be developed into clinically-viable tests for the early detection and clinical management of patients with colorectal cancer in the not so distant future.

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Androgen blockade based clinical trials landscape in triple negative breast cancer

Publication date: Available online 25 May 2018

Source: Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

Author(s): Yaqin Shi, Fang Yang, Doudou Huang, Xiaoxiang Guan

Abstract

Androgen receptor (AR) targeted treatment has shown promising preliminary results in triple negative breast cancer (TNBC). Identification of AR-associated signaling pathways is of great significance for in-depth understanding of their roles in pathogenesis of TNBC. To meet this objective, preclinical and clinical studies were conducted to clarify the biological interactions of AR signaling and combination strategies based on AR-targeted therapy. Biologically, AR signaling in TNBC which not only interacts with a network of key pathways, involving PI3K/AKT/mTOR, cell cycle, and DNA damage repair pathways, but mediates pivotal processes of tumor initiation and immunogenic modulation, may present an opportunity to overcome the insensitivity of single AR-targeted therapy. Research in investigating androgen-blockade based combination therapy in this aggressive tumor has demonstrated promising benefit in preclinical studies, and comparable clinical trials of combined strategies with CDK4/6 inhibitors, PI3K inhibition, chemotherapy, and immunotherapy, are ongoing. Accordingly, clinical interpretation of AR-related biological interactions, aiming at combined blockade of the signaling pathways may pave a new way for endocrine-based therapy in the treatment of TNBC.

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Mitochondria in cancer metabolism, an organelle whose time has come?

Publication date: Available online 26 May 2018

Source: Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

Author(s): Rebecca G. Anderson, Lais P. Ghiraldeli, Timothy S. Pardee

Abstract

Mitochondria have long been controversial organelles in cancer. Early discoveries in cancer metabolism placed much emphasis on cytosolic contributions. Initial debate focused on if mitochondria had a role in cancer formation and progression at all. More recently the contributions of mitochondria to cancer development and progression have become firmly established. This has led to the identification of novel targets and inhibitors being studied as new therapeutic approaches. This review will summarize the role of mitochondria in cancer and highlight several agents under development.

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The plasticity of pancreatic cancer metabolism in tumor progression and therapeutic resistance

Publication date: Available online 24 April 2018

Source: Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

Author(s): Douglas E. Biancur, Alec C. Kimmelman

Abstract

Pancreatic ductal adenocarcinoma (PDA) is an aggressive cancer that is highly refractory to the current standards of care. The difficulty in treating this disease is due to a number of different factors, including altered metabolism. In PDA, the metabolic rewiring favors anabolic reactions which supply the cancer cell with necessary cellular building blocks for unconstrained growth. Furthermore, PDA cells display high levels of basal autophagy and macropinocytosis. KRAS is the driving oncogene in PDA and many of the metabolic changes are downstream of its activation. Together, these unique pathways for nutrient utilization and acquisition result in metabolic plasticity enabling cells to rapidly adapt to nutrient and oxygen fluctuations. This remarkable adaptability has been implicated as a cause of the intense therapeutic resistance. In this review, we discuss metabolic pathways in PDA tumors and highlight how they contribute to the pathogenesis and treatment of the disease.

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MYC-induced metabolic stress and tumorigenesis

Publication date: Available online 20 May 2018

Source: Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

Author(s): Adam J. Wolpaw, Chi V. Dang

Abstract

The MYC oncogene is commonly altered across human cancers. Distinct from the normal MYC proto-oncogene, which is under tight transcriptional, translational, and post-translational control, deregulated oncogenic MYC drives imbalanced, non-linear amplification of transcription that results in oncogenic 'stress.' The term 'stress' had been a euphemism for our lack of mechanistic understanding, but synthesis of many studies over the past decade provides a more coherent picture of oncogenic MYC driving metastable cellular states, particularly altered metabolism, that activate and depend on cellular stress response pathways to allow for continued growth and survival. Both deregulated metabolism and these stress response pathways represent vulnerabilities that can be exploited therapeutically.

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Inorganic phosphate transporters in cancer: Functions, molecular mechanisms and possible clinical applications

Publication date: Available online 9 May 2018

Source: Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

Author(s): Marco Antônio Lacerda-Abreu, Thais Russo-Abrahão, Robson de Queiroz Monteiro, Franklin David Rumjanek, José Roberto Meyer-Fernandes

Abstract

Inorganic phosphate is one of the most essential nutrients for the maintenance of cell life. Because of its essential role in nutrient supplementation, the study of plasma membrane inorganic phosphate transporters in cancer biology has received much attention in recent years. Several studies suggest that these transporters are up-regulated in tumor cells and thus have been considered to be important promoters of tumor progression. Altered expression levels of inorganic phosphate transporters, such as NaPi-IIb (SLC34A2) and PiT-1 (SLC20A1), have been demonstrated. The purpose of this review article was to gather the relevant experimental records on inorganic phosphate transporters in tumors and to demonstrate the importance of these proteins in clinical applications. In this work, we demonstrate that for decades, the potential use of the inorganic phosphate transporter as an antigen for the diagnosis of tumor subtypes remained unknown. With the advancement in molecular biology techniques, phosphate transporters have been identified as being associated with cancer. In addition to their altered expression in cancer, several studies have demonstrated other functions of inorganic phosphate transporters, such as transceptors, rearrangements with oncogenes and modifications in the expression of ABC transporters, aiding in the process of proliferation and drug resistance.

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Metabolic reprogramming of the tumor microenvironment by p62 and its partners

Publication date: Available online 25 April 2018

Source: Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

Author(s): Miguel Reina-Campos, Phillip M. Shelton, Maria T. Diaz-Meco, Jorge Moscat

Abstract

The concerted metabolic reprogramming across cancer and normal cellular compartments of the tumor microenvironment can favor tumorigenesis by increasing the survival and proliferating capacities of transformed cells. p62 has emerged as a critical signaling adaptor, beyond its role in autophagy, by playing an intricate context-dependent role in metabolic reprogramming of the cell types of the tumor and stroma, which shapes the tumor microenvironment to control tumor progression. Focusing on metabolic adaptations, we review the cellular processes upstream and downstream of p62 that regulate how distinct cell types adapt to the challenging and evolving environmental conditions during tumor initiation and progression. In addition, we describe partners of p62 that, in a collaborative or independent manner, can also rewire cell metabolism. Finally, we discuss the potential therapeutic implications of targeting p62 in cancer, considering its multifaceted roles in diverse cell types of the tumor microenvironment.

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The pro-tumorigenic effects of metabolic alterations in glioblastoma including brain tumor initiating cells

Publication date: April 2018

Source: Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Volume 1869, Issue 2

Author(s): Catherine J. Libby, Anh Nhat Tran, Sarah E. Scott, Corinne Griguer, Anita B. Hjelmeland

Abstract

De-regulated cellular energetics is an emerging hallmark of cancer with alterations to glycolysis, oxidative phosphorylation, the pentose phosphate pathway, lipid oxidation and synthesis and amino acid metabolism. Understanding and targeting of metabolic reprogramming in cancers may yield new treatment options, but metabolic heterogeneity and plasticity complicate this strategy. One highly heterogeneous cancer for which current treatments ultimately fail is the deadly brain tumor glioblastoma. Therapeutic resistance, within glioblastoma and other solid tumors, is thought to be linked to subsets of tumor initiating cells, also known as cancer stem cells. Recent profiling of glioblastoma and brain tumor initiating cells reveals changes in metabolism, as compiled here, that may be more broadly applicable. We will summarize the profound role for metabolism in tumor progression and therapeutic resistance and discuss current approaches to target glioma metabolism to improve standard of care.

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Chaperoning the guardian of the genome. The two-faced role of molecular chaperones in p53 tumor suppressor action

Publication date: April 2018

Source: Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Volume 1869, Issue 2

Author(s): Bartosz Wawrzynow, Alicja Zylicz, Maciej Zylicz

Abstract

Organized networks of heat shock proteins, which possess molecular chaperone activity, protect cells from abrupt environmental changes. Additionally, molecular chaperones are essential during stress-free periods, where they moderate housekeeping functions. During tumorigenesis, these chaperone networks are extensively remodeled in such a way that they are advantageous to the transforming cell. Molecular chaperones by buffering critical elements of signaling pathways empower tumor evolution leading to chemoresistance of cancer cells. Controversially, the same molecular chaperones, which are indispensable for p53 in reaching its tumor suppressor potential, are beneficial in adopting an oncogenic gain of function phenotype when TP53 is mutated. On the molecular level, heat shock proteins by unwinding the mutant p53 protein expose aggregation-prone sites leading to the sequestration of other tumor suppressor proteins causing inhibition of apoptosis and chemoresistance. Therefore, within this review therapeutic approaches combining classical immuno- and/or chemotherapy with specific inhibition of selected molecular chaperones shall be discussed.

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Fusion genes: A promising tool combating against cancer

Publication date: April 2018

Source: Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Volume 1869, Issue 2

Author(s): Xiaofeng Dai, Rutaganda Theobard, Hongye Cheng, Mengtao Xing, Jianying Zhang

Abstract

The driving roles of fusion genes during tumorigenesis have been recognized for decades, with efficacies demonstrated in clinical diagnosis and targeted therapy. With advances in sequencing technologies and computational biology, a surge in the identification of fusion genes has been witnessed during the past decade. The discovery and presence of splicing based fusions in normal tissues have challenged our canonical conceptions on fusion genes and offered us novel medical opportunities. The specificity of fusion genes to neoplastic tissues and their diverse functionalities during carcinogenesis foster them as promising tools in the battle against cancer. It is time to re-visit and comb through our cutting-edge knowledge on fusion genes to accelerate clinical translation of these internal markers. Urged as such, we are encouraged to categorize fusion events according to mechanisms leading to their generation, oncological consequences and clinical implications, offer insights on fusion occurrence across tumors from the system level, highlight feasible practices in fusion-related pharmaceutical development, and identify understudied yet important niches that may lead future research trend in this field.

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Colorectal cancer prevention: Immune modulation taking the stage

Publication date: April 2018

Source: Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Volume 1869, Issue 2

Author(s): Rochelle Fletcher, Yi-Jun Wang, Robert E. Schoen, Olivera J. Finn, Jian Yu, Lin Zhang

Abstract

Prevention or early detection is one of the most promising strategies against colorectal cancer (CRC), the second leading cause of cancer death in the US. Recent studies indicate that antitumor immunity plays a key role in CRC prevention. Accumulating evidence suggests that immunosurveillance represents a critical barrier that emerging tumor cells have to overcome in order to sustain the course of tumor development. Virtually all of the agents with cancer preventive activity have been shown to have an immune modulating effect. A number of immunoprevention studies aimed at triggering antitumor immune response against early lesions have been performed, some of which have shown promising results. Furthermore, the recent success of immune checkpoint blockade therapy reinforces the notion that cancers including CRC can be effectively intervened via immune modulation including immune normalization, and has stimulated various immune-based combination prevention studies. This review summarizes recent advances to help better harness the immune system in CRC prevention.

https://ift.tt/2lTM3Ff

Mapping Active Gene-Regulatory Regions in Human Repopulating Long-Term HSCs

Publication date: 5 July 2018

Source: Cell Stem Cell, Volume 23, Issue 1

Author(s): Peer Wünsche, Elias S.P. Eckert, Tim Holland-Letz, Anna Paruzynski, Agnes Hotz-Wagenblatt, Raffaele Fronza, Tim Rath, Irene Gil-Farina, Manfred Schmidt, Christof von Kalle, Christoph Klein, Claudia R. Ball, Friederike Herbst, Hanno Glimm

Summary

Genes that regulate hematopoietic stem cell (HSC) self-renewal, proliferation, and differentiation are tightly controlled by regulatory regions. However, mapping such regions relies on surface markers and immunophenotypic definition of HSCs. Here, we use γ-retroviral integration sites (γRV ISs) from a gene therapy trial for 10 patients with Wiskott-Aldrich syndrome to mark active enhancers and promoters in functionally defined long-term repopulating HSCs. Integration site clusters showed the highest ATAC-seq signals at HSC-specific peaks and strongly correlated with hematopoietic risk variants. Tagged genes were significantly enriched for HSC gene sets. We were able to map over 3,000 HSC regulatory regions in late-contributing HSCs, and we used these data to identify miR-10a and miR-335 as two miRNAs regulating early hematopoiesis. In this study, we show that viral insertion sites can be used as molecular tags to assess chromatin conformation on functionally defined cell populations, thereby providing a genome-wide resource for regulatory regions in human repopulating long-term HSCs.

Graphical Abstract

https://ift.tt/2Kzj7RE

Mentoring the Next Generation: Fred Gage

Publication date: 5 July 2018

Source: Cell Stem Cell, Volume 23, Issue 1

Author(s):

Mentor-mentee relationships are essential for professional development, but developing these interpersonal skills is not often highlighted as a priority in scientific endeavors. In a yearlong series, Cell Stem Cell interviews prominent scientists who have prioritized mentorship over the years. Here, we chat with Dr. Fred Gage about his views.

https://ift.tt/2MTpYlt

Secretion of Shh by a Neurovascular Bundle Niche Supports Mesenchymal Stem Cell Homeostasis in the Adult Mouse Incisor

Publication date: 5 July 2018

Source: Cell Stem Cell, Volume 23, Issue 1

Author(s): Hu Zhao, Jifan Feng, Kerstin Seidel, Songtao Shi, Ophir Klein, Paul Sharpe, Yang Chai

https://ift.tt/2Kwu2LQ

Th17 Lymphocytes Induce Neuronal Cell Death in a Human iPSC-Based Model of Parkinson’s Disease

Publication date: 5 July 2018

Source: Cell Stem Cell, Volume 23, Issue 1

Author(s): Annika Sommer, Franz Maxreiter, Florian Krach, Tanja Fadler, Janina Grosch, Michele Maroni, Daniela Graef, Esther Eberhardt, Markus J. Riemenschneider, Gene W. Yeo, Zacharias Kohl, Wei Xiang, Fred H. Gage, Jürgen Winkler, Iryna Prots, Beate Winner

Summary

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive degeneration of midbrain neurons (MBNs). Recent evidence suggests contribution of the adaptive immune system in PD. Here, we show a role for human T lymphocytes as cell death inducers of induced pluripotent stem cell (iPSC)-derived MBNs in sporadic PD. Higher Th17 frequencies were found in the blood of PD patients and increased numbers of T lymphocytes were detected in postmortem PD brain tissues. We modeled this finding using autologous co-cultures of activated T lymphocytes and iPSC-derived MBNs of sporadic PD patients and controls. After co-culture with T lymphocytes or the addition of IL-17, PD iPSC-derived MBNs underwent increased neuronal death driven by upregulation of IL-17 receptor (IL-17R) and NFκB activation. Blockage of IL-17 or IL-17R, or the addition of the FDA-approved anti-IL-17 antibody, secukinumab, rescued the neuronal death. Our findings indicate a critical role for IL-17-producing T lymphocytes in sporadic PD.

Graphical Abstract

https://ift.tt/2KOoWK8

Skeletal Muscle Stem Cells from PSC-Derived Teratomas Have Functional Regenerative Capacity

Publication date: 5 July 2018

Source: Cell Stem Cell, Volume 23, Issue 1

Author(s): Sunny Sun-Kin Chan, Robert W. Arpke, Antonio Filareto, Ning Xie, Matthew P. Pappas, Jacqueline S. Penaloza, Rita C.R. Perlingeiro, Michael Kyba

Summary

Derivation of functional skeletal muscle stem cells from pluripotent cells without genetic modification has proven elusive. Here we show that teratomas formed in adult skeletal muscle differentiate in vivo to produce large numbers of α7-Integrin+ VCAM-1+ myogenic progenitors. When FACS-purified and transplanted into diseased muscles, mouse teratoma-derived myogenic progenitors demonstrate very high engraftment potential. As few as 40,000 cells can reconstitute ∼80% of the tibialis anterior muscle volume. Newly generated fibers are innervated, express adult myosins, and ameliorate dystrophy-related force deficit and fatigability. Teratoma-derived myogenic progenitors also contribute quiescent PAX7+ muscle stem cells, enabling long-term maintenance of regenerated muscle and allowing muscle regeneration in response to subsequent injuries. Transcriptional profiling reveals that teratoma-derived myogenic progenitors undergo embryonic-to-adult maturation when they contribute to the stem cell compartment of regenerated muscle. Thus, teratomas are a rich and accessible source of potent transplantable skeletal muscle stem cells.

Video Abstract

Graphical Abstract

https://ift.tt/2MRTCry

Recipes for Making Neurons using Combinatorial Forward Genetics

Publication date: 5 July 2018

Source: Cell Stem Cell, Volume 23, Issue 1

Author(s): Vania Broccoli, Mirko Luoni

In a recent issue of Nature, Tsunemoto et al. (2018) perform a systematic screening to identify several transcription factor pairs able to generate a variety of different induced neuronal cell populations that share a core neuronal signature, yet differ for specific molecular features.

https://ift.tt/2MOdXhg

The Regenerative Altruism of Hepatocytes and Cholangiocytes

Publication date: 5 July 2018

Source: Cell Stem Cell, Volume 23, Issue 1

Author(s): George K. Michalopoulos

In this issue of Cell Stem Cell and recently in Nature, Deng et al. (2018) and Schaub et al. (2018) (respectively) demonstrate that following acute liver injury, hepatocytes and cholangiocytes restore liver mass and function. When proliferative capacity of either cell type is impaired, the other cell type will transdifferentiate to restore full regeneration and hepatic histology.

https://ift.tt/2KwRWHf

Genotoxic Lemons Become Epigenomic Lemonade

Publication date: 5 July 2018

Source: Cell Stem Cell, Volume 23, Issue 1

Author(s): Stefan F. Cordes, Cynthia E. Dunbar

Active regulatory elements in hematopoietic stem cells (HSCs) are incompletely characterized, since extant approaches immunophenotypically define and isolate rare HSCs. In the current issue of Cell Stem Cell, Wünsche et al. (2018) use γ-retroviral insertion sites from a human gene therapy trial to identify the active enhancer landscape of functionally characterized HSCs.

https://ift.tt/2MRrgxH

Postmitotic Fate Refinement in the Subplate

Publication date: 5 July 2018

Source: Cell Stem Cell, Volume 23, Issue 1

Author(s): Mohammed A. Mostajo-Radji, Alex A. Pollen

How is the astonishing diversity of cortical neurons specified? In this issue of Cell Stem Cell, Ozair et al. (2018) leverage hPSC neural differentiation to show that projection neurons undergo prolonged sojourns in the subplate before migrating to deep layers, suggesting that pausing in the subplate may enable integration of intrinsic and extrinsic cues during postmitotic fate refinement.

https://ift.tt/2KLlGiV

Th17 Cells in Parkinson’s Disease: The Bane of the Midbrain

Publication date: 5 July 2018

Source: Cell Stem Cell, Volume 23, Issue 1

Author(s): Ashley C. Bolte, John R. Lukens

Emerging data implicate potential roles for T cells in Parkinson's disease (PD); however, direct evidence for human T cells in PD-associated neurodegeneration has been lacking. In this issue of Cell Stem Cell, Sommer et al. (2018) demonstrate that IL-17-producing T cells from sporadic PD patients promote cell death of patient iPSC-derived midbrain neurons.

https://ift.tt/2MS5zxc

Muscling in on the Awesome Proliferative Power of the Terrible Teratoma

Publication date: 5 July 2018

Source: Cell Stem Cell, Volume 23, Issue 1

Author(s): Alicia A. Cutler, Bradley B. Olwin

In this issue of Cell Stem Cell, Chan et al. (2018) report that in vivo differentiation of pluripotent stem cells in induced teratomas produces functional embryonic-like muscle stem cells. These purified muscle stem cells engraft with high efficiency and regenerate serially injured muscle.

https://ift.tt/2MOGtzy

Mitochondrial Shapeshifting Impacts AML Stemness and Differentiation

Publication date: 5 July 2018

Source: Cell Stem Cell, Volume 23, Issue 1

Author(s): Aaron D. Schimmer

In this issue of Cell Stem Cell, Pei et al. (2018) demonstrate that leukemic stem cells (LSCs) have enhanced mitochondrial fission, which is positively regulated by FIS1. FIS1 is necessary to maintain LSC function; thus, targeting its expression and mitochondrial fission is a novel approach to decrease stemness and increase differentiation in Acute Myeloid Leukemia.

https://ift.tt/2KCLnmo

Ultrasound-guided left lateral transversus abdominis plane block combined with rectus sheath block in peritoneal dialysis catheter placement

Abstract

This study assessed the utility of ultrasound-guided lateral transversus abdominis plane (TAP) block combined with rectus sheath (RS) block for peritoneal dialysis catheter placement surgery. Thirty consecutive patients with end-stage renal disease scheduled to have peritoneal dialysis catheter placement received a left lateral TAP block combined with RS block performed under ultrasound guidance. The TAP and RS blocks were, respectively, conducted with 15 ml of 0.5% ropivacaine and 10 ml of 0.5% ropivacaine. Pain intensity was evaluated by verbal rating scale during operation, and the degree of patient and surgeon satisfaction was qualified by a categorical scale. Twenty-nine patients received successful blocks without any other adjuvant anesthetic drugs. One patient required rescue analgesia with lidocaine infiltration. No complications related to regional anesthesia were noted. Ultrasound-guided left lateral TAP block combined with RS block can serve as the primary anesthetic modality for peritoneal dialysis catheter placement surgery.

https://ift.tt/2KzV2u0

CytoTECHnology: The benefits of technology in teaching

Cancer Cytopathology, EarlyView.


https://ift.tt/2u7RWCy

HPV RNA in situ hybridization can inform cervical cytology‐histology correlation

Cancer Cytopathology, EarlyView.


https://ift.tt/2lXVkw5

Prognostic factors in patients with metastatic spine tumors derived from lung cancer—a novel scoring system for predicting life expectancy

Abstract

Background

Recently, molecule-targeting and bone-modifying agents have improved the treatment outcomes of lung cancer-derived metastatic spine tumors. Therefore, the prognostic factors for such tumors were examined, and novel scoring systems for predicting the life expectancy of patients with such tumors were proposed.

Methods

In 207 patients with lung cancer-derived metastatic spine tumors (surgery 49; conservative therapy 158), we retrospectively examined the factors that influenced the post-treatment survival time (age, sex, the affected site, pathology, general condition, the number of extraspinal bone metastases, the number of spinal metastases, the presence/absence of major internal organ metastasis, paralysis state, the total Tokuhashi score, the serum alkaline phosphatase level, the serum carcinoembryonic antigen level, molecule-targeting drug treatment, and bone-modifying agent treatment). Based on the results, we devised novel scoring systems for predicting the prognosis of such patients.

Results

Univariate analyses showed that the pathology of the primary lung tumor, the patient's general condition and paralysis state, and the presence/absence of molecule-targeting drug treatment significantly influenced survival. We performed a Cox regression analysis of these four factors and developed criteria for a novel scoring system based on the patient's general condition and paralysis state, which exhibited significance in the regression analysis. A retrospective review indicated that the consistency rate between predicted life expectancy and actual survival was 67.3%. When criteria based on the four factors that exhibited significance in the univariate analyses were adopted, the consistency rate was 76.2%.

Conclusion

The patient's general condition and paralysis state, the pathology of the primary lung tumor, and molecule-targeting drug treatment influenced survival among patients with lung cancer-derived metastatic spine tumors. Novel scoring systems based on these four factors were proposed.

https://ift.tt/2KPgwSS

Review of the possible association between thyroid and breast carcinoma

Abstract

Background

Thyroid and breast cancer are two of the malignant diseases with highest incidence in females. Based on clinical experience, breast and thyroid cancer often occur metachronously or synchronously. Therefore, thyroid and breast cancer might share some common etiological factors. The relationship between these diseases has attracted substantial attention, and because these two glands are both regulated by the hypothalamic-pituitary axis, such a relationship is not surprising. A study of this relationship will be useful for obtaining a better understanding of the mechanism by which these two malignancies co-occur.

Main body

This study reviewed the progress in research on the roles of iodine intake, folate metabolism, obesity, gonadal hormones, and thyroid hormone in thyroid and breast cancer. These studies evaluating the etiological roles of these factors in linking breast and thyroid cancer might also improve our understanding and identify new therapeutic approaches, such as sodium/iodide symporter-mediated radioiodine therapy and thyroid-stimulating hormone receptor antagonists, for breast cancer. In addition, some specific treatments for each cancer, such as radiotherapy for breast cancer or radioactive iodine therapy for thyroid cancer, might be risk factors for secondary malignances, including breast and thyroid cancer.

Conclusions

Studies of the precise relationship between the co-occurrence of breast and thyroid cancer will certainly improve our understanding of the biological behaviors of these two malignancies and direct evidence-based clinical practice.

https://ift.tt/2MPyh1K

The Dutch national guideline on metastases and hematological malignancies localized within the spine; a multidisciplinary collaboration towards timely and proactive management

Publication date: September 2018

Source: Cancer Treatment Reviews, Volume 69

Author(s): Karlijn H.J. Groenen, Yvette M. van der Linden, Thea Brouwer, Sander P.D. Dijkstra, Alexander de Graeff, Paul R. Algra, Jos M.A. Kuijlen, Monique C. Minnema, Claudia Nijboer, Davey L.H. Poelma, Christa Rolf, Tebbe Sluis, Michel A.M.B. Terheggen, Alexandra C.M. van der Togt-van Leeuwen, Ronald H.M.A. Bartels, Walter Taal

Abstract

Here, we describe the development of a Dutch national guideline on metastases and hematological malignancies localized within the spine. The aim was to create a comprehensive guideline focusing on proactive management of these diseases, enabling healthcare professionals to weigh patient perspectives, life expectancy, and expected outcomes to make informed treatment recommendations. A national multidisciplinary panel consisting of clinicians, a nurse, a patient advocate, an epidemiologist, and a methodologist drafted the guideline. The important role of patients in the realization of the guideline enabled us to identify and address perceived shortcomings in patient care. The guideline covers not only metastatic epidural spinal cord compression, but also the treatment of uncomplicated metastases and hematological malignancies localized within the spine. The guideline is applicable in daily practice and provides an up-to-date and concise overview of the diagnostic and treatment possibilities for patients suffering from a disease that can have a serious impact on their quality of life. Suggestions for the practical implementation of patient care in hospitals are also provided, including approaches for pursuing proactive management. The crucial role of the patient in decision making is emphasized in this guideline.

https://ift.tt/2KREsVE

Chemotherapy and cognition: International cognition and cancer task force recommendations for harmonising preclinical research

Publication date: September 2018

Source: Cancer Treatment Reviews, Volume 69

Author(s): Gordon Winocur, Ian Johnston, Hélène Castel

Abstract

Cancer survivors who undergo chemotherapy for non-CNS tumours often report substantial cognitive disturbances that adversely affect quality of life, during and after treatment. The neurotoxic effects of anti-cancer drugs have been confirmed in clinical and pre-clinical research. Work with animals has also identified a range of factors and underlying mechanisms that contribute to chemotherapy-induced cognitive impairment. However, there is a continuing need to develop standard cognitive testing procedures for validation and comparison purposes, broaden the search for biological and neurochemical mechanisms, and develop improved animal models for investigating the combined effects of treatment, the disease, and other potential factors (e.g., age, stress). In this paper, a working group, formed under the auspices of the International Cognition and Cancer Task Force, reviews the state of pre-clinical research, formulates strategic priorities, and provides recommendations to guide animal research that meaningfully informs clinical investigations.

https://ift.tt/2KS39Ow

Fallopian tube tumorigenesis and clinical implications for ovarian cancer risk-reduction

Publication date: September 2018

Source: Cancer Treatment Reviews, Volume 69

Author(s): Allison A. Gockley, Kevin M. Elias

Abstract

Ovarian cancer remains the leading cause of gynecologic cancer death among American women. Prevention is the only proven approach to reduce the incidence of the disease. Oral contraception, tubal ligation, and risk-reducing salpingo-oophorectomy (rrBSO) for high-risk groups are all established risk reduction strategies. This paradigm is changing as recent biologic studies suggest that many ovarian cancers, especially high-grade serous ovarian cancers, originate in the distal end of the fallopian tube rather than the ovarian surface epithelium. A putative precursor lesion has been identified called the serous tubal intraepithelial carcinoma (STIC). Theoretically, removal of the fallopian tubes alone may prevent these lesions and prevent overt disease. Opportunistic salpingectomy during benign gynecologic surgery appears to be safe and may offer some protection from ovarian cancer without compromising ovarian endocrine function. Despite a lack of evidence for efficacy, several professional societies now recommend this approach for average-risk women. Whether salpingectomy can also serve as a temporizing measure to delay risk-reducing oophorectomy in women with a genetic predisposition to ovarian cancer remains to be seen. Several ongoing non-randomized clinical trials will test the feasibility of this approach. Therefore, the societal impact of increasing salpingectomy rates on ovarian cancer incidence will be an area of intense focus for the next 10–20 years.

https://ift.tt/2KREiO2

Checkpoint inhibitors as treatment for malignant gliomas: “A long way to the top”

Publication date: September 2018

Source: Cancer Treatment Reviews, Volume 69

Author(s): Matteo Simonelli, Pasquale Persico, Matteo Perrino, Paolo Andrea Zucali, Pierina Navarria, Federico Pessina, Marta Scorsetti, Lorenzo Bello, Armando Santoro

Abstract

Glioblastoma is the most common and lethal malignant brain tumor in adults, with a very poor prognosis of less than two years despite surgical resection followed by radiotherapy and chemotherapy. To date, targeted agents and antiangiogenic therapy have failed to show survival benefits and novel treatment approaches are urgently needed.

Immune checkpoint inhibitors have recently revolutionized the landscape of cancer immunotherapy achieving regulatory approvals for a number of other 'historically' resistant cancers. These exciting successes have generated great interest in investigating if these agents could be such effective also in brain tumors field. Moreover, the traditional dogma that considers the central nervous system (CNS) as an immune-privileged site lacking the potential for immunosurveillance has been challenged as it has become clear that the CNS is immunoactive. Critical barriers to an effective antitumor immunity in brain tumor patients are still represented by the peculiar CNS immunological milieu and the numerous systemic and local immunosuppressive forces exhibited by malignant gliomas to avoid immune recognition and cellular death.

This review describes the current status of checkpoint modulation as treatment for malignant gliomas. We start illustrating the compelling molecular and immunological rationale, than we show striking preclinical evidence of activity and discuss available data from prospective clinical trials. Furthermore, we explore the role of predictive biomarkers of responsiveness to checkpoint blockade in the context of gliomas, along with the development of combinatorial and potentially synergistic approaches with other established anti-cancer treatments or complementary immunotherapeutic modalities.

https://ift.tt/2KUVpeA

Long-term survival after liver metastasectomy in gastric cancer: Systematic review and meta-analysis of prognostic factors

Publication date: September 2018

Source: Cancer Treatment Reviews, Volume 69

Author(s): Francesco Montagnani, Francesca Crivelli, Giuseppe Aprile, Caterina Vivaldi, Irene Pecora, Rocco De Vivo, Mario Alberto Clerico, Lorenzo Fornaro

Abstract

Background

Despite the amelioration of systemic therapy, overall survival (OS) of metastatic gastric cancer (GC) patients remains poor. Liver is a common metastatic site and retrospective series suggest a potential OS benefit from hepatectomy, with interesting 5-year (5 y) and 10-year (10 y) OS rates in selected patients. We aim to evaluate the impact of liver resection and related prognostic factors on long-term outcome in this setting.

Methods

We searched Pubmed, EMBASE, and Abstracts/posters from international meetings since 1990. Data were extracted from publish papers. Random effects models meta-analyses and meta-regression models were built to assess 5yOS and the impact of different prognostic factor. Heterogeneity was assessed using between study variance, I² and Cochran's Q. Funnel plot were used to assess small study bias.

Results

Thirty-three observational studies (for a total of 1304 patients) were included. Our analysis demonstrates a 5yOS rate of 22% (95%CI: 18–26%) and 10yOS rate of 11% (95%CI: 7–18%) among patients undergoing radical hepatectomy. A favorable effect on OS was shown by several factors linked to primary cancer (lower T and N stage, no lympho-vascular or serosal invasion) and burden of hepatic disease (≤3 metastases, unilobar involvement, greatest lesion < 5 cm, negative resection margins). Moreover, lower CEA and CA19.9 levels and post-resection chemotherapy were associated with improved OS.

Conclusions

Surgical resection of liver metastases from GC seems associated with a significant chance of 5yOS and 10yOS and compares favourably with results of medical treatment alone. Prospective evaluation of this approach and validation of adequate selection criteria are needed.

https://ift.tt/2KyaCq2

Maintenance treatment of recurrent ovarian cancer: Is it ready for prime time?

Publication date: September 2018

Source: Cancer Treatment Reviews, Volume 69

Author(s): Paul DiSilvestro, Angeles Alvarez Secord

Abstract

Approximately 1% of women in the United States will be diagnosed with epithelial ovarian cancer (EOC) during their lifetime. It is most likely to present at a more advanced stage, requiring aggressive therapeutic measures, and most women will succumb to this illness. Due to advancements in therapy, the oncology community has begun to shift its focus to molecular targeted agents, alternative dosing schedules, and maintenance therapy. Women who achieve a response to initial adjuvant chemotherapy may be candidates for maintenance therapy, with the goal of inducing a lasting remission or prolonging the disease-free interval before recurrence. The rationale for maintenance therapy is to delay disease progression by eliminating residual, slowly-dying cancerous cells, or impeding cell turnover. This review discusses the goals of maintenance therapy for EOC with antiangiogenic agents or poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors, and reviews clinical studies that have demonstrated improvements in survival outcomes. The side-effect profiles for PARP inhibitors and the implications for preserving quality of life during maintenance therapy will also be discussed.

https://ift.tt/2KNlOuZ

It is finally time for adjuvant therapy in melanoma

Publication date: September 2018

Source: Cancer Treatment Reviews, Volume 69

Author(s): S. Napolitano, G. Brancaccio, G. Argenziano, E. Martinelli, F. Morgillo, F. Ciardiello, T. Troiani

Abstract

Although melanoma is amenable to early detection, there has been no decline in the mortality rate of this disease and the prognosis of patients with high-risk primary melanoma or with macroscopic nodal involvement remains poor. The best option for patients with higher-risk melanoma is to receive effective adjuvant therapy in order to reduce their chances of recurrence. Multiple systemic therapeutic agents have been tested as adjuvant therapy for melanoma with durable benefits seen only with interferon- to date. More recently ipilimumab at the high dose of 10 mg/kg has shown a significant improvement in terms of Relapse free survival and Overall survival for stage III melanoma patients but at a significant cost in terms of immune-related toxicities. More recently, novel treatment options have emerged. The results from the latest trials with immunotherapy (PD-1 inhibitors) and molecular targeted therapy (BRAF inhibitor + MEK inhibitor) have revolutionized the management of adjuvant treatment for melanoma. As the results from these trials will mature in the next years, a change in the landscape of adjuvant treatment for melanoma is expected, resulting in new challenges in treatment decisions such as optimizing patients' selection through predictive and prognostic biomarkers, and management of treatment related adverse events, in particular immune related toxicities.

https://ift.tt/2KJ7Rl7

The poor design of clinical trials of statins in oncology may explain their failure – Lessons for drug repurposing

Publication date: September 2018

Source: Cancer Treatment Reviews, Volume 69

Author(s): Marwan I. Abdullah, Elizabeth de Wolf, Mohammed J. Jawad, Alan Richardson

Abstract

Statins are widely used to treat hypercholesterolaemia. However, by inhibiting the production of mevalonate, they also reduce the production of several isoprenoids that are necessary for the function of small GTPase oncogenes such as Ras. As such, statins offer an attractive way to inhibit an "undruggable" target, suggesting that they may be usefully repurposed to treat cancer. However, despite numerous studies, there is still no consensus whether statins are useful in the oncology arena. Numerous preclinical studies have provided evidence justifying the evaluation of statins in cancer patients. Some retrospective studies of patients taking statins to control cholesterol have identified a reduced risk of cancer mortality. However, prospective clinical studies have mostly not been successful. We believe that this has occurred because many of the prospective clinical trials have been poorly designed. Many of these trials have failed to take into account some or all of the factors identified in preclinical studies that are likely to be necessary for statins to be efficacious. We suggest an improved trial design which takes these factors into account. Importantly, we suggest that the design of clinical trials of drugs which are being considered for repurposing should not assume it is appropriate to use them in the same way as they are used in their original indication. Rather, such trials deserve to be informed by preclinical studies that are comparable to those for any novel drug.

https://ift.tt/2KS36lO

Vitamin D in melanoma: Controversies and potential role in combination with immune check-point inhibitors

Publication date: September 2018

Source: Cancer Treatment Reviews, Volume 69

Author(s): Luigia Stefania Stucci, Stella D'Oronzo, Marco Tucci, Antonella Macerollo, Simone Ribero, Francesco Spagnolo, Elena Marra, Virginia Picasso, Laura Orgiano, Riccardo Marconcini, Francesco De Rosa, Lorenza Di Guardo, Giulia Galli, Sara Gandini, Raffaele Palmirotta, Giuseppe Palmieri, Paola Queirolo, Francesco Silvestris, for the Italian Melanoma Intergroup (IMI)

Abstract

The role of vitamin D in melanoma is still controversial. Although several Authors described a correlation between vitamin D deficiency and poor survival in metastatic melanoma patients, clinical trials exploring the effects of vitamin D supplementation in this clinical setting were mostly inconclusive.

However, recent evidence suggests that vitamin D exerts both anti-proliferative effects on tumor cells and immune-modulating activities, that have been widely explored in auto-immune disorders. On the one hand, vitamin D has been shown to inhibit T-helper17 lymphocytes, notoriously involved in the pathogenesis of immune-related adverse events (iAEs) which complicate immune-checkpoint inhibitor (ICI) treatment. On the other hand, vitamin D up-regulates PDL-1 expression on both epithelial and immune cells, suggesting a synergic effect in combination with ICIs, for which further investigation is needed.

https://ift.tt/2KwIqnv

Novel urinary biomarkers for the detection of bladder cancer: A systematic review

Publication date: September 2018

Source: Cancer Treatment Reviews, Volume 69

Author(s): Wei Shen Tan, Wei Phin Tan, Mae-Yen Tan, Pramit Khetrapal, Liqin Dong, Patricia deWinter, Andrew Feber, John D. Kelly

Abstract

Background

Urinary biomarkers for the diagnosis of bladder cancer represents an area of considerable research which has been tested in both patients presenting with haematuria and non-muscle invasive bladder cancer patients requiring surveillance cystoscopy. In this systematic review, we identify and appraise the diagnostic sensitive and specificity of reported novel biomarkers of different 'omic' class and highlight promising biomarkers investigated to date.

Methods

A MEDLINE/Pubmed systematic search was performed between January 2013 and July 2017 using the following keywords: (bladder cancer OR transitional cell carcinoma OR urothelial cell carcinoma) AND (detection OR diagnosis) AND urine AND (biomarker OR assay). All studies had a minimum of 20 patients in both bladder cancer and control arms and reported sensitivity and/or specificity and/or receiver operating characteristics (ROC) curve. QUADAS-2 tool was used to assess risk of bias and applicability of studies. The search protocol was registered in the PROSPERO database (CRD42016049918).

Results

Systematic search yielded 115 reports were included for analysis. In single target biomarkers had a sensitivity of 2–94%, specificity of 46–100%, positive predictive value (PPV) of 47–100% and negative predictive value (NPV) of 21–94%. Multi-target biomarkers achieved a sensitivity of 24–100%, specificity of 48–100%, PPV of 42–95% and NPV of 32–100%. 50 studies achieved a sensitivity and specificity of ≥80%. Protein (n = 59) and transcriptomic (n = 21) biomarkers represents the most studied biomarkers. Multi-target biomarker panels had a better diagnostic accuracy compared to single biomarker targets. Urinary cytology with urinary biomarkers improved the diagnostic ability of the biomarker. The sensitivity and specificity of biomarkers were higher for primary diagnosis compared to patients in the surveillance setting. Most studies were case control studies and did not have a predefined threshold to determine a positive test result indicating a possible risk of bias.

Conclusion

This comprehensive systematic review provides an update on urinary biomarkers of different 'omic' class and highlights promising biomarkers. Few biomarkers achieve a high sensitivity and negative predictive value. Such biomarkers will require external validation in a prospective observational setting before adoption in clinical practice.

https://ift.tt/2IXuugC

Tobacco smoking and survival after a prostate cancer diagnosis: A systematic review and meta-analysis

Publication date: Available online 4 July 2018

Source: Cancer Treatment Reviews

Author(s): Ellie Darcey, Terry Boyle

Abstract

Background

While a number of studies indicating tobacco smoking has a detrimental impact on survival and recurrence after a prostate cancer diagnosis, there has been no quantitative review of this literature and it is unclear whether tobacco smoking affects clinical populations differentially. We conducted a systematic review and meta-analysis to investigate the associations between tobacco smoking and overall (OM) and prostate cancer-specific (PSM) mortality and recurrence after a prostate cancer diagnosis.

Methods

EMBASE and ISI Web of Science were searched for English-language studies, published up to August 17, 2017, which conducted a survival analysis to estimate the association between tobacco smoking and OM, PSM and/or recurrence. A random-effects meta-analysis was conducted to estimate the summary hazard ratios (HRs) for the associations between tobacco smoking and the three outcomes.

Results

A total of 28 studies met the inclusion criteria. The results of the primary meta-analysis indicate current smokers have significantly poorer overall survival (Summary HR=1.96, 95% CI=1.69, 2.28), prostate cancer-specific survival (Summary HR=1.79, 95%CI=1.47, 2.20) and recurrence-free survival (Summary HR =1.48, 95%CI=1.28, 1.72) than never smokers. Similar results were found in population-based studies and in studies conducted in specific clinical populations.

Conclusions

The results of this systematic review and meta-analysis indicate that tobacco smoking at prostate cancer diagnosis is associated with a significantly increased risk of overall mortality, prostate-cancer specific mortality and recurrence. We recommend future studies collect more detailed information about tobacco smoking to further understanding of the association between tobacco smoking and PCa prognosis. In addition, further research should concentrate on the impact of smoking cessation post-diagnosis and post-treatment on prognosis, and the feasibility and effectiveness of smoking cessation programs.

https://ift.tt/2KRUeAc

Optimisation of treatment with lenvatinib in radioactive iodine-refractory differentiated thyroid cancer

Publication date: Available online 2 July 2018

Source: Cancer Treatment Reviews

Author(s): Jaume Capdevila, Kate Newbold, Lisa Licitra, Aron Popovtzer, Francesc Josep Moreso Mateo, José Zamorano, Michael Kreissl, Javier Aller, Enrique Grande

Abstract

Lenvatinib has been approved for the treatment of advanced differentiated thyroid cancer (DTC) refractory to radioactive iodine (RAI) following the results of the SELECT trial which demonstrated a significant increase in progression-free survival and a high response rates. The data reported for lenvatinib in RAI-refractory DTC (RAI-R DTC) are the most significant to date in this patient population, with a RECIST objective response rate above 60% and almost 80% reduction in the risk of disease progression. Because the first indication in oncology for lenvatinib is specifically in RAI-R DTC, a period of familiarisation with its safety and efficacy profile is required.

This review includes a series of specific recommendations for optimising the management of RAI-R DTC with lenvatinib, as well as specific guidelines for minimising the incidence and severity of adverse events (AEs), which enable dose intensity to be increased and this way maximise the benefits of the drug in the patient population treated. These recommendations were defined at a meeting of experts of different specialities, reviewing available scientific evidence on the drug, as well as their own direct personal experience in daily clinical practice.

For toxicity to be properly managed, a multidisciplinary approach is required in which the different medical services, nursing staff and the patient and their careers are all involved. It is essential to assess the suitability of patients who are candidates for lenvatinib, as well as their clinical and physiological status prior to treatment. They must then be closely monitored to prevent and detect possible AEs. The main objective should be to maintain the dose that obtains the maximum therapeutic effect, discontinuing the treatment only if the toxicity becomes unmanageable or there is no clinical benefit.

https://ift.tt/2KUko1F

Assessment of the risk of antiangiogenic agents before and after surgery

Publication date: July 2018

Source: Cancer Treatment Reviews, Volume 68

Author(s): Christina E. Bailey, Alexander A. Parikh

Abstract

Angiogenesis plays a critical role in the growth, progression, and metastasis of numerous solid tumor types, and thus, antiangiogenic agents have been studied for many years as potential therapeutic agents. Many different antiangiogenic agents, including monoclonal antibodies and multi-targeted tyrosine kinase inhibitors (TKIs), have been approved for various oncology indications, and promising clinical activity has been demonstrated. However, some of these agents have also been associated with serious safety concerns. Because angiogenesis is an important step in the wound healing process, agents targeting the angiogenesis pathway may interfere with wound healing, thus increasing the risk of surgical wound complications, such as dehiscence, surgical site bleeding, and wound infection. Nevertheless, antiangiogenic agents can be safely used in the perioperative setting if oncologists and surgeons are educated on the biology and pharmacokinetics of these agents. This review discusses the available published literature regarding surgical complications associated with the use of antiangiogenic agents and provides updated clinical recommendations on the optimal timing between surgery and antiangiogenic therapy. Due to the paucity of data surrounding this topic, current and future clinical trials need to evaluate prospectively the potential risks for surgical complications associated with antiangiogenic therapies to establish specific guidelines for their safe and effective use within the surgical oncology community.

Graphical abstract

Note that only VEGF/VEGFR, FGF/FGFR, and PDGF/PDGFR are depicted for the purposes of this figure.

https://ift.tt/2KxFtTu

Clinical development of HER3-targeting monoclonal antibodies: Perils and progress

Publication date: July 2018

Source: Cancer Treatment Reviews, Volume 68

Author(s): Wolfgang Jacob, Ian James, Max Hasmann, Martin Weisser

Abstract

The human epidermal growth factor receptor (HER) family consists of four transmembrane receptor tyrosine kinases: epidermal growth factor receptor (EGFR), HER2, HER3, and HER4. They are part of a complex signalling network and stimulate intracellular pathways regulating cell growth and differentiation. So far, monoclonal antibodies (mAbs) and small molecule tyrosine kinase inhibitors targeting EGFR and HER2 have been developed and approved. Recently, focus has turned to HER3 as it may play an important role in resistance to EGFR- and HER2-targeting therapies. HER3-targeting agents have been undergoing clinical evaluation for the last 10 years and currently thirteen mAbs are in phase 1 or 2 clinical studies. Single agent activity has proven to be limited, however, the tolerability was favourable. Thus, combinations of HER3-binding mAbs with other HER-targeting therapies or chemotherapies have been pursued in various solid tumor entities. Data indicate that the HER3-binding ligand heregulin may serve as a response prediction marker for HER3-targeting therapy. Within this review the current status of clinical development of HER3-targeting compounds is described.

https://ift.tt/2KPC95u

Borderline resectable pancreatic cancer. Challenges and controversies

Publication date: July 2018

Source: Cancer Treatment Reviews, Volume 68

Author(s): Luis Sabater, Elena Muñoz, Susana Roselló, Dimitri Dorcaratto, Marina Garcés-Albir, Marisol Huerta, Desamparados Roda, María Carmen Gómez-Mateo, Antonio Ferrández-Izquierdo, Antonio Darder, Andrés Cervantes

Abstract

Pancreatic cancer is a dismal disease with an increasing incidence. Despite the majority of patients are not candidates for curative surgery, a subgroup of patients classified as borderline resectable pancreatic cancer can be selected in whom a sequential strategy of neoadjuvant therapy followed by surgery can provide better outcomes. Multidisciplinary approach and surgical pancreatic expertise are essential for successfully treating these patients. However, the lack of consensual definitions and therapies make the results of studies very difficult to interpret and hard to be implemented in some settings. In this article, we review the challenges of borderline resectable pancreatic cancer, the complexity of its management and controversies and point out where further research and international cooperation for a consensus strategy is urgently needed.

https://ift.tt/2IVxQki

Androgen receptor in triple negative breast cancer: A potential target for the targetless subtype

Publication date: July 2018

Source: Cancer Treatment Reviews, Volume 68

Author(s): L. Gerratana, D. Basile, G. Buono, S. De Placido, M. Giuliano, S. Minichillo, A. Coinu, F. Martorana, I. De Santo, L. Del Mastro, M. De Laurentiis, F. Puglisi, G. Arpino

Abstract

Triple negative breast cancer (TNBC) represents the 15–20% of all breast cancers (BC) and is characterized by a very aggressive behavior. Recent data suggest that TNBC is not a single disease, but it is rather an umbrella for different ontology-profiles such as basal like 1 and 2, mesenchymal, and the luminal androgen receptor (LAR). The LAR subtype is characterized by the expression of the Androgen Receptor (AR) and its downstream effects. Notwithstanding the role of the AR in several signaling pathways, its impact on a biological and clinical standpoint is still controversial. The LAR subtype has been associated with better prognosis, less chemotherapy responsiveness and lower pathologic complete response after neoadjuvant treatment. Clinical evidence suggests a role for anti-androgen therapies such as bicalutamide, enzalutamide and abiraterone, offering an interesting chemo-free alternative for chemo-unresponsive patients, and therefore potentially shifting current treatment strategies.

https://ift.tt/2KCccav

Presentation and diagnosis of patients with type 3 von Willebrand disease in resources-limited laboratory

Publication date: Available online 3 July 2018

Source: Hematology/Oncology and Stem Cell Therapy

Author(s): Abbas Hashim Abdulsalam, Yusra Ghiath, Nidhal Alrahal

Abstract

Von Willebrand disease (VWD) is a bleeding disorder that results from decreased von Willebrand factor (VWF) activity <0.30 iu/mL. Therefore, the diagnosis of type 3 VWD in patients with bleeding requires finding a VWF:Ag and/or VWF:platelet ristocetin cofactor (RiCof) <0.03 iu/mL, no further testing is usually necessary. This is a cohort study that included 64 patients with type 3 VWD who were presented and diagnosed at the National Center of Hematology (NCH) from October 2014 to October 2016. In this study the sensitivity of VWF:Ag is only 78%, the sensitivity of VWF:RiCof is 92% of diagnosed cases. From our results it can be concluded that patients with type 3 VWD are usually presented with moderate/severe mucocutaneous bleeding that is associated with prolonged bleeding time test of >10 min and a family history of similar type of bleeding. This fact was frequently utilized to provisionally diagnose several members of the same family, forming a cohort of patients that is larger than the number of objectively-diagnosed patients included in this study, when they cannot afford to be all tested with VWF:Ag/VWF:RiCof.

https://ift.tt/2KSqgsr

Acquired factor X deficiency in light-chain (AL) amyloidosis is rare and associated with advanced disease

Publication date: Available online 28 June 2018

Source: Hematology/Oncology and Stem Cell Therapy

Author(s): Gina Patel, Parameswaran Hari, Aniko Szabo, Lisa Rein, Lisa Baumann Kreuziger, Saurabh Chhabra, Binod Dhakal, Anita D'Souza

Abstract

Systemic light-chain (AL) amyloidosis can lead to an acquired coagulopathy secondary to acquired factor X (aFX) deficiency. However, it is not very clear who develops aFX deficiency in AL amyloidosis. We, therefore, undertook this single-center study to better characterize AL amyloidosis-associated aFX deficiency. Out of 121 AL patients who had FX testing at the time of their first evaluation at our institution, including 17 patients on warfarin at the time of testing, 10 out of 104 patients (9.6%) with systemic AL amyloidosis were found to have FX levels below 50%. aFX deficiency was associated with advanced stage of AL amyloidosis and elevated cardiac biomarkers. Lower FX activity, advanced stage, and cardiac involvement by disease were associated with higher hazard of death on univariate analysis. On multivariate analysis, stage of AL amyloidosis was the only significant predictor of survival. Median survival time of patients with FX deficiency was 9.3 months compared with 118.4 months in those without the deficiency. We conclude that while aFX deficiency is rare in systemic AL amyloidosis, it is a marker of advanced disease.

https://ift.tt/2KxIOlv

Retrospective evaluation of fidaxomicin versus oral vancomycin for treatment of Clostridium difficile infections in allogeneic stem cell transplant

Publication date: Available online 18 June 2018

Source: Hematology/Oncology and Stem Cell Therapy

Author(s): Laura Prohaska, Zahra Mahmoudjafari, Leyla Shune, Anurag Singh, Tara Lin, Sunil Abhyankar, Siddhartha Ganguly, Dennis Grauer, Joseph McGuirk, Lisa Clough

Abstract

Objective/background

Clostridium difficile infection (CDI) is a potential complication during hematopoietic stem cell transplantation (HSCT), and no specific recommendations exist regarding treatment of CDI in allogeneic SCT patients. Use of metronidazole and oral vancomycin has been associated with clinical failure. Fidaxomicin has previously been found noninferior to the use of oral vancomycin for the treatment of CDI, and no studies have compared the use of oral vancomycin with fidaxomicin for the treatment of CDI in allogeneic SCT.

Methods

This retrospective chart review included 96 allogeneic SCT recipients who developed CDI within 100 days following transplantation. Participants were treated with oral vancomycin (n = 52) or fidaxomicin (n = 44). The primary outcome was clinical cure, defined as no need for further retreatment 2 days following completion of initial CDI treatment. Secondary outcomes were global cure, treatment failure, and recurrent disease.

Results

No differences in clinical cure were observed between patients receiving oral vancomycin or fidaxomicin (75% vs. 75%, p = 1.00). Secondary outcomes were similar between oral vancomycin and fidaxomicin in regards to global cure (66% vs. 67%, p = .508), treatment failure (28% vs. 27%, p = .571), and recurrent disease (7% vs. 5%, p = .747). In a subanalysis of individuals that developed acute graft-versus-host disease following CDI, the difference in mean onset of acute graft-versus-host disease was 21.03 days in the oral vancomycin group versus 32.88 days in the fidaxomicin group (p = .0031).

Conclusion

The findings of this study suggest that oral vancomycin and fidaxomicin are comparable options for CDI treatment in allogeneic SCT patients within 100 days following transplant.

https://ift.tt/2IVW6Tl

Granulocytic sarcoma and mediastinal germ cell tumor: A common cell of origin?

Publication date: Available online 15 June 2018

Source: Hematology/Oncology and Stem Cell Therapy

Author(s): Sarbajit Mukherjee, Sami Ibrahimi, Teresa Scordino, Mohamad Cherry

https://ift.tt/2KOXJHt

Philadelphia chromosome-positive lymphoblastic lymphoma—Is it rare or underdiagnosed?

Publication date: Available online 15 June 2018

Source: Hematology/Oncology and Stem Cell Therapy

Author(s): Ahmad Alshomar, Riad El Fakih

Abstract

Lymphoblastic lymphomas (LBLs) are neoplasms of precursor B and T cells; they are considered in the same spectrum as precursor B and T cell acute lymphoblastic leukemia (ALL). The World Health Organization classification classifies both LBL and ALL as one disease entity. While chromosome abnormalities are well defined with all of their therapeutic and prognostic implications in ALL, these are not well studied in LBL. Here, we describe a case of Philadelphia chromosome-positive LBL and review the available literature regarding this entity.

https://ift.tt/2J0WGzm

Parvovırus-induced thrombocytopenıa

Publication date: Available online 15 June 2018

Source: Hematology/Oncology and Stem Cell Therapy

Author(s): Burak Furkan Demir, Aysenur Karahan Meteris, Gokhan Yirgin, Mustafa Comoglu, Bilal Katipoglu, Nisbet Yılmaz, Ihsan Ates

https://ift.tt/2KOOneS

Rosai-Dorfman disease masquerading as Uveal Melanoma: Case report and review of literature

Publication date: Available online 15 June 2018

Source: Hematology/Oncology and Stem Cell Therapy

Author(s): Yacoub A. Yousef, Maysa Al-Hussaini, Rashed Nazzal, Ghadeer Abdeen, Ibrahim Alnawaiseh, Khaleel Alrawashdeh

Abstract

Objective/Background

Intra ocular Rosai-Dorfman disease (RDD) is an extremely rare disease. We are reporting the first case of RDD presenting as ciliary body mass mimicking ciliary body melanoma, and we are reviewing the English literature reporting on cases of RDD presented with intraocular disease.

Methods

An 18-year-old lady presented with loss of vision in the right eye, and was found to have intraocular mass lesion. She was diagnosed clinically and radiologically as a case of ciliary body melanoma associated with total retinal detachment.

Results

Histopathological sections and stains proved to be intraocular RDD. Review of the literature revealed three cases of intraocular RDD; two of them had choroid thickening associated with serous retinal detachment, and one presented with intraocular mass mimicking choroid melanoma. Two of the three cases were enucleated. Our case is the first case in English literature of intraocular ciliary body RDD, mimicking ciliary body melanoma.

Conclusion

RDD can present as an intraocular mass that mimics ciliary body melanoma. This case emphasizes the importance of diagnostic biopsy before considering the final therapy in unclear cases, mainly when associated with unusual systemic features like lymphadenopathy.

https://ift.tt/2IVr0eF

CD209-336A/G promotor polymorphism and its clinical associations in sickle cell disease Egyptian Pediatric patients

Publication date: June 2018

Source: Hematology/Oncology and Stem Cell Therapy, Volume 11, Issue 2

Author(s): Rasha Abdel-Raouf Afifi, Dina Kamal, Riham El. Sayed, Sherif M.M. Ekladious, Gehan H. Shaheen, Sherif M. Yousry, Rania Elsayed Hussein

Abstract

Objectives

To detect the frequency of CD209 A>G polymorphism in sickle cell disease (SCD) Egyptian patients and to evaluate the use of CD209 A>G polymorphism as a genetic predictor of SCD clinical heterogeneity.

Methods

A total of 100 Egyptian children with SCD and 100 Egyptian controls were tested for CD209 A>G polymorphism and were followed up prospectively between June 2012 and December 2014.

Results

Comparison of CD209 A>G polymorphism among cases and controls did not show statistically significant difference (p = .742). In addition, comparison of the allelic frequency did not show statistically significant difference (p = .738). Infections occurred more frequently among the heterozygous genotype (AG; 60.5%) and homozygous genotype (GG; 75%) patients than among the wild (AA) genotype (24.1%; p < .001). The use of hydroxyurea treatment was significantly higher among the wild (AA) genotype (47%) than the heterozygous (AG; 21%) and homozygous (GG; 5%) genotypes (p = .003).

Conclusion

We found no significant difference between our population of Egyptian SCD cases and controls regarding CD209 A>G polymorphism. Infections occurred more frequently among the heterozygous genotype (AG) and homozygous genotype (GG) patients.

https://ift.tt/2KMB1zG

Study of platelet activation, hypercoagulable state, and the association with pulmonary hypertension in children with β-thalassemia

Publication date: June 2018

Source: Hematology/Oncology and Stem Cell Therapy, Volume 11, Issue 2

Author(s): Mahmoud Alhosiny Fayed, Hesham El-Sayed Abdel-Hady, Mona Mohammed Hafez, Osama Saad Salama, Youssef Abdelhalim Al-Tonbary

Abstract

Background

The increased survival rate of thalassemic patients has led to unmasking of management related complications which were infrequently encountered.

Objective

Study the increased coagulation and platelet activation in children with β-thalassemia, to analyze the factors that lead to such hypercoagulable state and to study pulmonary hypertension (PH) in conjunction with platelet activation and hypercoagulable state in children with β-thalassemia.

Methods

36 Egyptian children with β-thalassemia with a mean age of 9.9 years (±4.7 SD). In addition, 20 healthy Egyptian children matched for age and sex were enrolled as a control group. Both were subjected to clinical and laboratory assessments. Echocardiography was done to the patient group and PH was diagnosed based on calculated mean pulmonary artery pressure [MPAP] >25 mmHg.

Results

We found that, mean ± SD serum P-selectin level (platelet activator marker) was significantly higher in thalassemic patients (2337 ± 566 pg/ml) in comparison to controls (1467 ± 247 pg/ml) (P < 0.001). Mean serum protein-C and antithrombin-III levels were significantly lower in thalassemic patients (1.2 ± 1.3 µg/ml, 27.3 ± 7.5 mg/dl) in comparison to controls (2.3 ± 1.3 µg/ml, 35.1 ± 4.1 mg/dl) (P = 0.003 and <0.001) respectively. PH was detected in 17 (47.2%) patients and it was significantly associated with splenectomy (P = 0.01) and non-transfusion dependent thalassemia (NTDT) (P = 0.04). PH was positively correlated with serum levels of P-selectin (r = 0.38, P = 0.02), fibrinogen (r = 0.41, P = 0.01) and negatively correlated with serum protein-C level (r = −0.48, P = 0.003).

Conclusion

A chronic hypercoagulable state and platelet activation is present in children with β-thalassemia. Splenectomy and transfusion infrequency are the main risk factors noted to be associated with such hypercoagulable state and platelet activation and consequently the PH among our thalassemic patients.

https://ift.tt/2IWMyaE

Reduced intensity is preferred over myeloablative conditioning allogeneic HCT in chronic lymphocytic leukemia whenever indicated: A systematic review/meta-analysis

Publication date: June 2018

Source: Hematology/Oncology and Stem Cell Therapy, Volume 11, Issue 2

Author(s): Mohamed A. Kharfan-Dabaja, Nour Moukalled, Tea Reljic, Jessica El-Asmar, Ambuj Kumar

Abstract

Despite availability of new and more effective therapies for chronic lymphocytic leukemia, presently this disease remains incurable unless eligible patients are offered an allogeneic hematopoietic cell transplant. Recent published clinical practice recommendations on behalf of the American Society for Blood and Marrow Transplantation relegated the role of for allogeneic hematopoietic cell transplantation to later stages of the disease. To our knowledge, no randomized controlled trial has been performed to date comparing myeloablative versus reduced intensity conditioning regimens in chronic lymphocytic leukemia patients eligible for the procedure. We performed a systematic review/meta-analysis to assess the efficacy of allogeneic hematopoietic cell transplantation when using myeloablative or reduced intensity conditioning regimens. We report the results in accordance to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Based on lower non-relapse mortality and slightly better overall survival rates, reduced intensity conditioning regimens appear to be the most desirable choice whenever the procedure is indicated for this disease. It appears highly unlikely that a RCT will be ever performed comparing reduced intensity vs. myeloablative allogeneic hematopoietic cell transplantation in chronic lymphocytic leukemia. In the absence of such a study, results of this systematic review/meta-analysis represent the best available evidence supporting this recommendation whenever indicated in patients with chronic lymphocytic leukemia.

https://ift.tt/2KARqIb

Plasma cell myeloma with Auer rode like inclusions

Publication date: June 2018

Source: Hematology/Oncology and Stem Cell Therapy, Volume 11, Issue 2

Author(s): Nour AlMozain, Tarek Owaidah

https://ift.tt/2KTQcEd

Anemia in patient with primary hyperoxaluria and bone marrow involvement by oxalate crystals

Publication date: June 2018

Source: Hematology/Oncology and Stem Cell Therapy, Volume 11, Issue 2

Author(s): Vitaliy Mykytiv, Fiz Campoy Garcia

Abstract

We present a rare case of anaemia secondary to bone marrow infiltration by oxalate crystals and renal failure in a patient diagnosed with primary hyperoxaluria. In our case, the anaemia was recovered after the double liver and kidney transplantation, the latter was performed on two occasions after the failure of the first graft.

https://ift.tt/2KARebV

Acute promyelocytic leukemia with increased bone marrow reticulin fibrosis: Description of three cases and review of the literature

Publication date: June 2018

Source: Hematology/Oncology and Stem Cell Therapy, Volume 11, Issue 2

Author(s): Iman Abou Dalle, Samer Nassif, Ali Bazarbachi

Abstract

Pathologic increase in bone marrow reticulin fibrosis can be present in many malignant hematopoietic diseases. In acute leukemia, one-third of patients have some degree of marrow reticulin fibrosis at presentation, which is thought to be related to cytokine release from blasts. Marrow fibrosis is particularly common in acute megakaryoblastic leukemia, while this change is rarely seen in acute promyelocytic leukemia. Six case reports of acute promyelocytic leukemia with marrow reticulin fibrosis have been described so far in the literature. Herein, we present three cases of classical acute promyelocytic leukemia with increased marrow reticulin fibrosis encountered in our institution, summarizing their clinicopathologic features, treatment, and outcome to date. Awareness of the features of acute promyelocytic leukemia with marrow reticulin fibrosis is important as it may guide treatment options.

https://ift.tt/2KCxxAk

Haploidentical transplantation as a promising therapy for relapsed hemophagocytic lymphohistiocytosis in an older adult patient

Publication date: June 2018

Source: Hematology/Oncology and Stem Cell Therapy, Volume 11, Issue 2

Author(s): Ernesto Ayala, Denise LaFave, Taiga Nishihori, Mohamed A. Kharfan-Dabaja

Abstract

Hemophagocytic lymphohistiocytosis (HLH) is a rare but severe and often overwhelming systemic hyper-inflammatory syndrome generally presenting with unexplained fevers, hepatosplenomegaly, and progressive multi-organ dysfunction. Treatment of HLH has two major goals: Halting the triggering event and controlling the overactive immune system. However, patients with primary or recurrent secondary HLH should subsequently undergo allogeneic HCT for long lasting disease remission. Hereby we present the case of a 69 years old man with recurrent HLH who underwent a reduced intensity conditioning of fludarabine, cyclophosphamide and low dose total body irradiation followed by a haploidentical marrow graft and post-transplantation cyclophosphamide (PTCy), tacrolimus and mycophenolate mofetil as GVHD prophylaxis. He achieved a durable remission of HLH symptoms despite persistent myeloid mixed chimerism.

The use of haploidentical donors and PTCy as tolerance inducing regimen is feasible in HLH. The achievement of mixed donor chimerism may be enough to control the clinical manifestations and to cure HLH.

https://ift.tt/2IWG7EG